This is a 371 of International Application PCT/EP99/01673, with an international filing date of Mar. 15, 1999.
This invention relates to an apparatus for dispensing precisely measured small quantities of fluid and, more particularly, to dispensing such fluid quickly and with high accuracy and repeatability, particularly for chemical analysis purposes.
For purposes of analyzing fluids, particularly body fluids such as blood or urine, to evaluate the condition of the fluids and detect the presence of diseases, it is common practice to add to small quantities of the body fluids other chemicals which may react with the fluids in such a way that the fluids can be analyzed by an electro-mechanical analyzing machine such as a particle analyzing system sold by Partec GmbH, Muenster, Germany under the trademark Partec PAS II. For example, a sample of blood taken from a patient is divided into several parts, each typically being about 100 xcexcl (microliters) in volume. To each sample may be added three or more chemicals such as monoclonal antibodies of different types an possibly other strains or reagents, the resulting combinations are stirred and allowed to incubate for a selected interval of time. The process of adding these chemicals is usually referred to as pipetting. The resulting mixture is then ready to be pumped into the analyzer which provides information about the numbers of particles, their condition, etc. in ways which are well known per se. The resulting mixture may also be subjected to other forms of analysis, depending upon the kind of condition which is being sought.
There are several problems associated with this process. Because of the fact that the body fluids, particularly blood or serum, can carry viral and other substances which are dangerous to the individuals performing the analysis, efforts have been made to enclose the fluids so that the workers are not exposed to these fluids. In addition, efforts have been made to automate the processes to further reduce exposure and also improve the accuracy and precision of the chemical additions, partly to minimize the occasional human error.
One such effort involves the use of programmed, robotic arms which essentially mimic the motion of a human arm. A rack of test tubes containing fluids to be analyzed is placed in the vicinity of a programmed titrating machine, the tubes being arranged in the rack in a carefully selected order. Vials of additives such as monoclonal antibodies and other reagent materials are then placed in locations accessible to the machine arm. An arm, which carries a titrating tip, then goes through the same process as would be performed manually by a human operator: the tip is inserted into a vial containing one of the additives and sucks in a small quantity of additive. The arm then moves to the appropriate one of the test tubes and injects the additive into the tube. Before taking the next additive, the titrating tip must be washed. The arm then goes to the next additive, transfers a small quantity to the next test tube, is washed, and so on until all of the test tubes have received the desired quantities of the additives.
A system such as this has the advantage over manual operations that human error is reduced and the quantities of additives added to the various test tubes is reasonably accurate, i.e., within about 20%. The process can also be made more efficient by adding a first additive to all of those test tubes designated to receive that additive before washing and going on to the next one. All of this is under computer control, the computer being programmable to designate which tubes are to receive which additives.
However, the system also has serious disadvantages. In particular, it is not possible to effectively operate such a system with the vials and other apparatus closed in such a way that workers in the vicinity are isolated from the substances in the test tubes or other apparatus. Thus, if dangerous substances may, or are known to, be present, the workers themselves must be protected with special isolation clothing.
In addition, much time is consumed by this process. With a rack of thirty-six test tubes and four or five additives with different permutations of additives designated for the tubes, the machine can take hours to complete the process. Even with complex machines using two or three arms concurrently, which appears to be the practical maximum, the process can take one and one-half hours. In addition, the need to wash the titrators involves considerable waste of expensive materials. The monoclonal antibodies, in particular, are quite expensive and each washing necessitates that some of this valuable material is lost. Also, if dangerous substances such as radioactive markers are used, the washing step requires that special care to be taken in disposing of the waste water. Still further, the mechanical apparatus involved in an arm system requires long rapid movements, placing significant demands on the equipment which must be maintained. The apparatus is rather fragile and maintenance is a significant expense and removes the equipment from use at regular intervals. No other reasonably efficient automated system is known to exist.
Pipetting is also used in fields other than laboratory medicine, such as other chemical processes, food production and processing and fermentation technology. The amounts of liquid handled in these fields varies from very small up to large amounts of liquid, e.g., from amounts measured in microliters to liters. For the larger amounts, pipetting is not generally used, but for the smaller amounts, particularly in a laboratory context, it is very common.
Briefly described, the invention comprises an apparatus for dispensing a measured quantity of a liquid comprising a container holding a quantity of liquid to be measured and dispensed, a conduit having an inlet end and an outlet end and including a measuring section having a predetermined volume and a dispensing tip at the outlet end, and sensor means for determining when the measuring section contains liquid. A passage is provided for delivering liquid from the container to the conduit inlet end. A source of air under pressure urges liquid from the container to the conduit. A first valve is in the passage. A source of air under pressure is connected to the conduit. A second valve controls delivery of air to the conduit from the source. Control means connected to the sensor means and to the first and second valves sequentially closes the second valve and opens the first valve to cause flow of liquid from the container to the conduit until the sensor means determines that the measuring section contains liquid, and then closes the first valve and opens the second valve to admit air to the conduit, thereby expelling a measured quantity of liquid from the dispensing tip.